Prof Marcus Munafo - Nature or nurture?

Prof Marcus Munafo, university of Bristol

Kat - Also at the Genetics Society meeting we heard from Professor Marcus Munafo, from the University of Bristol. He’s trying to get to the bottom of another big question in biology - how much of our personality is down to nature, and how much is nurture. I started by asking him what we know so far about how our genes shape our responses to events around us.

Marcus - In my opinion, there aren’t many findings that are really robust at least within the context of psychiatric genotypes. So, there has been a lot of interest in for example, whether specific genes influence your sensitivity to stressful life events or in terms of the impact of those stressful life events and your risk of depression, or whether other specific genes specifically impact on the risk of cannabis use leading to Schizophrenia or Schizophrenia-like symptoms. Those stories are very compelling because of course, we want to be able to identify environmental risk factors and in particular, identify people who are most sensitive to them. But the difficulty is that many of those findings have proved hard to reproduce, that you have one initial study which looks very promising but then as other people try to reproduce that finding, the evidence becomes much less consistent.

Kat - And you mentioned stressful life events. I mean, I'm just about to move house. I'm finding that quite stressful, but someone might think, that's just moving. That's fine, but they might think that a divorce or a terrible accident is stressful. How do we define these kind of events? Surely, that's another layer of complexity?

Marcus - Well, that's exactly right and it’s the kind of thing that psychologists like myself often get quite animated about. You know, how do we measure these things? Do we want to focus on a projected measurement where people just report things, things that have happened to them or do we want to focus on the subjective impact of those things, so one person might find moving house very stressful and another person might not find it so stressful? If you just asked someone, “Have you moved house?” then you have a measure of whether or not that thing happened to them, but not necessarily what the impact of that potentially stressful life event on that person was.

Kat - And some of the talks we’ve heard about, they have used animal models of animal learning and animal reward. Can animal models tell us anything about this because presumably, it’s a bit easier to control the situations that animals are in?

Marcus - So, one of the great advantages in principle of animal models is exactly that, that you can control the environment much more closely and then you can modify that environment in a parametric way to see what the impact of introducing stress is to animal to a job perhaps genetically identical or from the same strains. And that's great in principle but actually, as more evidence has emerged, it’s become clear that what we think of as a highly controlled environment, still does contain a certain amount of variability. So for example, across different experiments, you might have different people handling the animals, different researchers running one experiment or the next experiment. And it seems that even factors like that which we try to control as much as possible can have an impact on the genetic effects that we observed. And we can do as much as we can to train people to behave as consistently as possible when they're in that situation of being a researcher. But we can only do that to a degree. We can automate as many processes as possible, but even then there's going to be stochastic variability in the environment that the animals are in - just random fluctuations in the environment that they find themselves in - that might have an important impact. And so, part of the difficulty is that there's just so much complexity in terms of the nature of the environmental exposures that even in those controlled environments, there may be too much complexity for us to pick out reliable gene environment interactions that we can reproduce over multiple experiments.

Kat - And it’s sounding to me like the picture is very complex. The things that happen to us are very complex, are very individual. Our own genetic makeup is individual. What is the future for this kind of research, trying to unpick nature versus nurture?

Marcus - Well, I think the first step is to proceed with the ongoing efforts that exist to identify genetic variants that are directly associated with these outcomes. I think that's the most robust starting point. These very large studies that combine data collaboratively to identify common and increasingly rare genetic variants that are directly associated with our outcomes of interest. Once we’ve got a better understanding of what the clear, robust, direct genetic associations are with these outcomes of interest, and we know what the environmental exposures are that make a difference, then we can start to look at the interplay between the two, with a bit more confidence that both of the main effects that we’re looking at are robust. There’ll always going to be technological advances. So, we’re moving already from genome wide association studies through to whole genome sequencing, for example, which is going to become common place in the next few years. But there's also increasing interest in the extent at which we can improve the measurements that we take, improve the precision of the phenotypes that we measure and refine the outcomes that we use in the environmental exposures that we use to much more precisely capture what we’ve been feeling and what we’ve been experiencing. And that then should improve our ability to detect these genetic effects, these environmental effects, and hopefully, ultimately, they interplay.

Kat - What's the kind of long term goal for this because obviously, understanding whether something is more nature or more nurture and the interplay of our genes in our environment, what would be the aim of this knowledge? What could we do with it?

Marcus - There are a few different aims and what your aim is will depend partly in your perspectives. So, understanding the genetic antecedents of mental health problems and psychiatric illness will hopefully tell us more about the underlying neurobiology and may, in principle identify new drug targets for example. Understanding more about environmental factors that play a role will allow us to again, potentially develop interventions, but also identify at-risk groups. And both of those are important goals in their own right. It’s not clear to me at least whether gene environment interactions are actually going to add that much to either of those efforts because of the limitations that exist at the moment in our ability to identify robust replicable interaction effects just because of the sheer complexity of the system that we’re dealing with. So at the moment, I think we’re on a much firmer ground when we look for direct effects, main effects and it becomes much more complex when we start to look for interaction effects.

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